Lauren Averett Byers, MD

Aggressive lung cancers called pulmonary high-grade neuroendocrine carcinomas (hgNECs), including large-cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), account for about 20% of lung cancers. Current treatment approaches are initially effective; however, the benefit is short-lived, and relapse occurs with ultimately resistance to all treatment options. Average life expectancy is only one year from diagnosis, highlighting the urgency of improving therapeutic options. Treatment resistance is driven by increasing tumor diversity (cells from the same tumor that are different) that steadily shifts in favor of emerging cancer cells resistant to available treatments. A tailored approach that accounts for these diverse cancer cells is critical to developing therapies capable of inducing long-term remission, or even cures, in these patients. We are using a radical approach to target diverse cell populations using their unique protein signatures to identify resistant cells and deliver chemotherapy directly.

Pierre Massion Lung Cancer Discovery Award

Update: In the first year of the project, we ran experiments to see which surface proteins are present in small cell lung cancer (SCLC) patients that can be targeted with current therapies. We also used a technique called mass spectrometry to discover new potential targets. We tested two FDA-approved precision-based cancer therapies (antibody drug conjugates, or ADCs), trastuzumab deruxtecan (T-Dxd) and sacituzumab govitecan (SG). We found that both strongly blocked the growth of SCLC cell lines. We are continuing to look for additional markers that could predict how well these drugs will work. We also examined the treatment potential of combining different approaches to achieve a broader tumor coverage across different types of tumors. We tested the combined effect of the cancer therapy DLL3 CAR-T and either HER2- or TROP2 ADCs. We found that the combination was more effective in reducing cell viability than either single agent.